ELL2, a new member of an ELL family of RNA polymerase II elongation factors

Abstract

We recently isolated an RNA polymerase II elongation factor from rat liver nuclei and found it to be homologous to the product of the human ELL gene, a frequent target for translocations in acute myeloid leukemia. To further our understanding of the possible role(s) of ELL in transcriptional regulation and human disease, we initiated a search for ELL-related proteins. In this report we describe molecular cloning, expression, and characterization of human ELL2, a novel RNA polymerase II elongation factor 49% identical and 66% similar to ELL. Mechanistic studies indicate that ELL2 and ELL possess similar transcriptional activities. Structure-function studies localize the ELL2 elongation activation domain to an ELL2 N-terminal region that is highly homologous to ELL. Finally, Northern blot analysis reveals that the ELL2 and ELL genes are transcribed in many of the same tissues, but that the ratio of their transcripts exhibits tissue-to-tissue variation, raising the possibility that ELL2 and ELL may not perform completely general functions, but, instead, may perform gene-or tissue-specific functions.

Microarray coupled to quantitative RT–PCR analysis of androgen-regulated genes in human LNCaP prostate cancer cells

“…TWIST1, a bHLH transcription factor that is upregulated in prostate cancer (Kwok et al, 2005), was upregulated 1.9-4.3-fold at 24 h by the other ligands. ELL2 is an RNA polymerase II elongation factor (Shilatifard et al, 1997), which interacts with the transcription factor EAF2 (ELL associated factor 2) (Simone et al, 2003). Interestingly, ELL2 and EAF2 genes show strong co-regulation, clustering together in the R1881 time course and in the expression profile in response to the other AR ligands.…”

U19/Eaf2 knockout causes lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostatic intraepithelial neoplasia

“…ELL was discovered as a fusion partner of MLL in the t(11; 19) (q23; p13.1) chromosomal translocation associated with acute myeloid leukemia (Thirman et al, 1994). ELL binds to RNA polymerase II and acts as a transcription elongation factor whose targeted deletion leads to embryonic lethality in mice (Shilatifard et al, 1996(Shilatifard et al, , 1997aMitani et al, 2000). Eaf2 also appears to be important during embryogenesis, particularly for eye development (Li et al, 2003;Maurus et al, 2005).…”

RNA Polymerase II Elongation Control

“…Based on their homology to ELL1, ELL2 and ELL3 were identified and shown to have similar elongation stimulatory activity in vitro (116,117). While ELL2 is expressed in many of the same tissues as ELL1, ELL3 is a testis-specific factor.…”